The invention relates to reducing hair growth in mammals, particularly for cosmetic purposes.
A main function of mammalian hair is to provide environmental protection. However, that function has largely been lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face.
Various procedures have been employed to remove unwanted hair, including shaving, electrolysis, depilatory creams or lotions, waxing, plucking, and therapeutic antiandrogens. These conventional procedures generally have drawbacks associated with them. Shaving, for instance, can cause nicks and cuts, and can leave a perception of an increase in the rate of hair regrowth. Shaving also can leave an undesirable stubble. Electrolysis, on the other hand, can keep a treated area free of hair for prolonged periods of time, but can be expensive, painful, and sometimes leaves scarring. Depilatory creams, though very effective, typically are not recommended for frequent use due to their high irritancy potential. Waxing and plucking can cause pain, discomfort, and poor removal of short hair. Finally, antiandrogens--which have been used to treat female hirsutism--can have unwanted side effects.
It has previously been disclosed that the rate and character of hair growth can be altered by applying to the skin inhibitors of certain enzymes. These inhibitors include inhibitors of 5-alpha reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Breuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. No. 5,095,007; Ahluwalia et al., U.S. Pat. No. 5,096,911; and Shander et al., U.S. Pat. No. 5,132,293.
Protein-tyrosine kinases (PTKs) are a class of enzymes that catalyze the transfer of the terminal phosphate from adenosine triphosphate (ATP) to the phenolic hydroxyl group of the amino acid tyrosine in substrate proteins (Malarkey et. al., Biochem. J. 309:361-375, 1995). These enzymes are normally present in one of two forms, a transmembrane receptor that binds growth factors and a cytoplasmic kinase that is involved in the signal transduction from other receptors.
Many transmembrane growth factor receptors possess PTK activity. Initiation of this activity following binding of an extracellular growth factor is the first step in cellular signal transduction pathway. The initial activation of the receptor protein-tyrosine kinase after a growth factor binding is manifested by autophosphorylation, which may cause conformational alterations exposing the active site to external substrates. This substrate activation in turn transmits the signal downstream. The binding of epidermal growth factor (EGF) at the extracellular binding domain is an example of the signaling process.
Central to the function of protein-tyrosine kinases is the recognition and binding of a nucleoside triphosphate (usually ATP), and a tyrosyl containing protein substrate. Several classes of protein kinase inhibitors have been described (Casnellie, Advances in Pharmacology 22:167-205, 1991; Burke, Drugs of the Future 17:119-131, 1992). They include agents that prevent the nucleotide (e.g., ATP) binding to PTKs; that prevent the substrate binding at the peptide binding site; and agents that decrease the catalytic efficiency by some other mechanism, e.g., binding to the allosteric regulatory site.